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Pancreatic glucagonoma associated with necrolytic migratory erythema: case report and clinical review
Poster Session, Sunday 29 January 2017
Abstracts
among Indian patients. This genetic difference observed between two population groups within the same continent might be attributable to increased population heterogeneity and admixture of ethnicities among Indians. Therefore, it necessitates the analysis of other documented/novel mutations involved in the genesis of insulinoma. No conflict of interest. 1516A NETs: Less common − still misunderstood
POSTER
N. Jervis1 , C. Bouvier2 . 1 NET Patient Foundation, Patient Advocacy and Support, Leamington Spa, United Kingdom; 2 NET Patient Foundation, Co-founder and CEO, Leamington Spa, United Kingdom Neuroendocrine Tumours (NETs) have long been considered rare cancers, with a high percentage of late diagnosis and incurability. Rare, less common, cancers pose a unique set of challenges: late or incorrect diagnosis, accessing clinical expertise and appropriate treatments, paucity in available patient information and difficulties in carrying out clinical studies due to the small number of patients. According to the definition of the project Surveillance of Rare Cancers in Europe (RARECARE), rare cancers are those with an incidence <6/100,000/year. However, recent work, supported by the NET Patient Foundation, undertaken by Public Health England reports an almost doubling of incidence of NETs, compared to previous figures, of 8:100,000 (prevalence of 35−40:100,000). So whilst, by definition, no longer rare − issues experienced by those with a NET remain the same. Materials and Methods: A critical review of the first published global survey of NET patient experienceand subsequent UK survey was undertaken − with comparison made with the UK National Cancer Patient Experience Survey (NET patients were not included). Further information was obtained by undertaking a thematic analysis of calls received by the NET Patient Foundation (the only UK NET patient charity) over the past 12 months. Results: Key themes identified included late diagnosis − with NET Patients reporting significantly more frequent visits to primary care prior to referral for investigation, delayed referral on to NET specialist centres, with more than 60% having metastatic disease by time of definitive diagnosis. A perceived lack of awareness and knowledge amongst both the general population and medical community about NETs − the exception being where patients were seen at a NET specialist centre. NET patients appear to be less likely to receive information on their disease, treatments, support groups and charities than those with common cancers (<50% compared with >80%). Conclusion: Despite improvements reported in patient experience for more common cancers, NET patients, alongside others with less common cancers, continue to experience deficits in care related to limited awareness, lack of knowledge, delayed accurate and timely diagnosis and therefore more difficulty in accessing appropriate care. No conflict of interest. 1517 POSTER Pancreatic glucagonoma associated with necrolytic migratory erythema: case report and clinical review
Surgery was indicated, and preoperative nutrition rich in amino acids were introduced, and thromboembolism prophylaxis. Two weeks later the skin lesions healed completely. Body-caudal pancreatectomy and total splenectomy were performed with spleen autotransplantation in greater omentum. Pathology report indicated a tumor in the pancreatic alpha cells. IHC showed expression of glucagon and chromogranin A in tumor cells (diagnosis of glucagonoma). In the postoperative period there was an improvement of glucose tolerance curve and normalization of serum levels of glucagon were observed, as well as evidence of splenic metabolism in the scintigraphy. Patient received outpatient follow-up for 10 years, without clinical complications. Conclusion: Glucagonoma syndrome is a paraneoplastic syndrome with a characteristic triad composed by: pancreatic tumor secreting glucagon, DM, and NME. Early recognition and correct diagnosis of NME is important because it can be the only manifestation of the GS. Other clinical features include weight loss, anemia, cheilitis, diarrhea, neurologic and psychiatric symptom and signs, and thromboembolic phenomena. Complete resection of the tumor is the best treatment. Patients who underwent resection had longer median survival than patients who did not receive surgery, even when diagnosed with later stages of disease. No conflict of interest. 1518 POSTER Predictive value of baseline hematology parameters on outcome of 177 Lu-DOTATOC-PRRT A. Kluge1 , R. Baum2 , H. Kulkarni2 , K. Niepsch2 , N. Bitterlich3 , M. Sayeg2 , U. Schorr-Neufing4 , C. Van Echteld5 . 1 ABX-CRO Advanced Pharmaceutical Services, General Management, Dresden, Germany; 2 Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Bad Berka, Germany; 3 ABX-CRO Advanced Pharmaceutical Services, Biostatistics, Dresden, Germany; 4 ABX-CRO Advanced Pharmaceutical Services, Regulatory Affairs, Dresden, Germany; 5 ABX-CRO Advanced Pharmaceutical Services, Pre-clinical & Pharmacy, Dresden, Germany Background: In external beam radiotherapy it has been well established that improved tissue oxygenation increases therapy efficacy, likely mediated by oxygen derived free radicals. Additionally, emerging evidence suggests immuno-stimulatory effects of radiotherapy through activation of lymphocytes. In peptide receptor radiotherapy (PRRT), the relevance of tissue oxygenation and immuno-stimulation have not been evaluated to date. Therefore, we compared baselineoweverHhematology parameters with PRRT efficacy. Material and Methods: After baseline hematology and laboratory evaluation, 56 patients with metastasized, progressive and DOTATOC uptake positive neuroendocrine tumors (NET) (50% gastroenteral, 26.8% pancreatic, 23.2% other primaries) were consecutively treated with 177 LuDOTATOC and analyzed retrospectively. Patients received on average 2.1 (range 1−4) cycles of 177 Lu-DOTATOC as 7.0 GBq (median) doses at 3-monthly intervals. Efficacy was analyzed based on RECIST and best response was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) in relation to baseline hematology parameters.
D. Cardoso1 , A. Cardoso1 , F. Cardoso Filho1 . 1 General Hospital of Fortaleza, Surgery Department, Fortaleza, Brazil Background: Glucagonoma is the rarest pancreatic neuroendocrine tumor (PNET) which is often heralded by paraneoplastic phenomena, with estimated incidence of 1 in 20 million. Necrolytic migratory erythema (NME) is a rare skin disorder and the hallmark clinical finding in glucagonoma syndrome (GS), it is present in almost 70% of patients. The key features of the GS are NME and diabetes mellitus (DM). Its diagnosis requires elevated serum glucagon level and imaging confirming pancreatic tumor. Tail of the pancreas is the most common site, and generally large due to late detection. Late diagnosis is common, mainly because of the extreme rarity of the tumor. Approximately half of patients will have metastatic disease by the time the diagnose is made, and the most common site is the liver. Because its slow growth, even patients with metastasis may achieve long survival. Case presentation: Male, 56 yo, had diffuse erythematous lesions in lower trunk, inguinal region, and lower limbs for nine years without remission after multiple admissions, and medical treatments. Abdominal ultrasound was requested, evidencing a mass on pancreatic topography. Abdominal CT was performed and hyperdense mass was confirmed on body-tail pancreatic of 10.0x9.0 cm with mild degree of contrast enhancement. Laboratory tests: presence of anemia, abnormal glucose tolerance test, reduced albumin and total protein levels, and amino acids quite diminished.
S151
CR PR SD PD PKW
Patients Hb (g/dl) (N)
Erythrocytes Leukocytes Lymphocytes Neutrophils Platelets (%) (103 cells/ml) (106 cells/ml) (103 cells/ml) (%)
9 10 18 19
4.64±0.54 4.35±0.49 4.38±0.55 4.19±0.65 <0.001
8.03±1.08 8.02±0.89 7.85±0.84 7.04±0.77 0.007
6.46±1.87 6.92±2.36 7.08±2.11 8.48±3.61 0.286
33.8±7.4 27.7±10.1 26.6±10.5 14.8±9.4 <0.001
53.8±10.1 61.3±10.7 60.6±12.3 73.1±13.4 0.006
299±98 228±61 252±72 337±170 0.093
Results: Hematology parameters are presented as mean ± standard deviation. The non-parametric Kruskal–Wallis test was used to detect significant differences. Post-hoc analysis with the least significant method was used to evaluate differences between groups. For all parameters with PKW < 0.01, the PD group was significantly different from all other groups. Conclusions: The significant positive correlations between PRRT outcome and baseline hemoglobin content, baseline erythrocyte cell count and baseline lymphocyte cell count are compatible with a cascade of free radical damage followed by immune activation. As the lymphocyte and neutrophil cell counts result from a differential white blood cell count, it is not surprising that we find an inverse correlation between PRRT outcome and neutrophil cell count. No correlation between PRRT outcome and leukocytes or platelets was found. Our results suggest that optimization of hemoglobin content prior to PRRT may be beneficial for therapy efficacy. No conflict of interest.
Abstracts
among Indian patients. This genetic difference observed between two population groups within the same continent might be attributable to increased population heterogeneity and admixture of ethnicities among Indians. Therefore, it necessitates the analysis of other documented/novel mutations involved in the genesis of insulinoma. No conflict of interest. 1516A NETs: Less common − still misunderstood
POSTER
N. Jervis1 , C. Bouvier2 . 1 NET Patient Foundation, Patient Advocacy and Support, Leamington Spa, United Kingdom; 2 NET Patient Foundation, Co-founder and CEO, Leamington Spa, United Kingdom Neuroendocrine Tumours (NETs) have long been considered rare cancers, with a high percentage of late diagnosis and incurability. Rare, less common, cancers pose a unique set of challenges: late or incorrect diagnosis, accessing clinical expertise and appropriate treatments, paucity in available patient information and difficulties in carrying out clinical studies due to the small number of patients. According to the definition of the project Surveillance of Rare Cancers in Europe (RARECARE), rare cancers are those with an incidence <6/100,000/year. However, recent work, supported by the NET Patient Foundation, undertaken by Public Health England reports an almost doubling of incidence of NETs, compared to previous figures, of 8:100,000 (prevalence of 35−40:100,000). So whilst, by definition, no longer rare − issues experienced by those with a NET remain the same. Materials and Methods: A critical review of the first published global survey of NET patient experienceand subsequent UK survey was undertaken − with comparison made with the UK National Cancer Patient Experience Survey (NET patients were not included). Further information was obtained by undertaking a thematic analysis of calls received by the NET Patient Foundation (the only UK NET patient charity) over the past 12 months. Results: Key themes identified included late diagnosis − with NET Patients reporting significantly more frequent visits to primary care prior to referral for investigation, delayed referral on to NET specialist centres, with more than 60% having metastatic disease by time of definitive diagnosis. A perceived lack of awareness and knowledge amongst both the general population and medical community about NETs − the exception being where patients were seen at a NET specialist centre. NET patients appear to be less likely to receive information on their disease, treatments, support groups and charities than those with common cancers (<50% compared with >80%). Conclusion: Despite improvements reported in patient experience for more common cancers, NET patients, alongside others with less common cancers, continue to experience deficits in care related to limited awareness, lack of knowledge, delayed accurate and timely diagnosis and therefore more difficulty in accessing appropriate care. No conflict of interest. 1517 POSTER Pancreatic glucagonoma associated with necrolytic migratory erythema: case report and clinical review
Surgery was indicated, and preoperative nutrition rich in amino acids were introduced, and thromboembolism prophylaxis. Two weeks later the skin lesions healed completely. Body-caudal pancreatectomy and total splenectomy were performed with spleen autotransplantation in greater omentum. Pathology report indicated a tumor in the pancreatic alpha cells. IHC showed expression of glucagon and chromogranin A in tumor cells (diagnosis of glucagonoma). In the postoperative period there was an improvement of glucose tolerance curve and normalization of serum levels of glucagon were observed, as well as evidence of splenic metabolism in the scintigraphy. Patient received outpatient follow-up for 10 years, without clinical complications. Conclusion: Glucagonoma syndrome is a paraneoplastic syndrome with a characteristic triad composed by: pancreatic tumor secreting glucagon, DM, and NME. Early recognition and correct diagnosis of NME is important because it can be the only manifestation of the GS. Other clinical features include weight loss, anemia, cheilitis, diarrhea, neurologic and psychiatric symptom and signs, and thromboembolic phenomena. Complete resection of the tumor is the best treatment. Patients who underwent resection had longer median survival than patients who did not receive surgery, even when diagnosed with later stages of disease. No conflict of interest. 1518 POSTER Predictive value of baseline hematology parameters on outcome of 177 Lu-DOTATOC-PRRT A. Kluge1 , R. Baum2 , H. Kulkarni2 , K. Niepsch2 , N. Bitterlich3 , M. Sayeg2 , U. Schorr-Neufing4 , C. Van Echteld5 . 1 ABX-CRO Advanced Pharmaceutical Services, General Management, Dresden, Germany; 2 Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Bad Berka, Germany; 3 ABX-CRO Advanced Pharmaceutical Services, Biostatistics, Dresden, Germany; 4 ABX-CRO Advanced Pharmaceutical Services, Regulatory Affairs, Dresden, Germany; 5 ABX-CRO Advanced Pharmaceutical Services, Pre-clinical & Pharmacy, Dresden, Germany Background: In external beam radiotherapy it has been well established that improved tissue oxygenation increases therapy efficacy, likely mediated by oxygen derived free radicals. Additionally, emerging evidence suggests immuno-stimulatory effects of radiotherapy through activation of lymphocytes. In peptide receptor radiotherapy (PRRT), the relevance of tissue oxygenation and immuno-stimulation have not been evaluated to date. Therefore, we compared baselineoweverHhematology parameters with PRRT efficacy. Material and Methods: After baseline hematology and laboratory evaluation, 56 patients with metastasized, progressive and DOTATOC uptake positive neuroendocrine tumors (NET) (50% gastroenteral, 26.8% pancreatic, 23.2% other primaries) were consecutively treated with 177 LuDOTATOC and analyzed retrospectively. Patients received on average 2.1 (range 1−4) cycles of 177 Lu-DOTATOC as 7.0 GBq (median) doses at 3-monthly intervals. Efficacy was analyzed based on RECIST and best response was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) in relation to baseline hematology parameters.
D. Cardoso1 , A. Cardoso1 , F. Cardoso Filho1 . 1 General Hospital of Fortaleza, Surgery Department, Fortaleza, Brazil Background: Glucagonoma is the rarest pancreatic neuroendocrine tumor (PNET) which is often heralded by paraneoplastic phenomena, with estimated incidence of 1 in 20 million. Necrolytic migratory erythema (NME) is a rare skin disorder and the hallmark clinical finding in glucagonoma syndrome (GS), it is present in almost 70% of patients. The key features of the GS are NME and diabetes mellitus (DM). Its diagnosis requires elevated serum glucagon level and imaging confirming pancreatic tumor. Tail of the pancreas is the most common site, and generally large due to late detection. Late diagnosis is common, mainly because of the extreme rarity of the tumor. Approximately half of patients will have metastatic disease by the time the diagnose is made, and the most common site is the liver. Because its slow growth, even patients with metastasis may achieve long survival. Case presentation: Male, 56 yo, had diffuse erythematous lesions in lower trunk, inguinal region, and lower limbs for nine years without remission after multiple admissions, and medical treatments. Abdominal ultrasound was requested, evidencing a mass on pancreatic topography. Abdominal CT was performed and hyperdense mass was confirmed on body-tail pancreatic of 10.0x9.0 cm with mild degree of contrast enhancement. Laboratory tests: presence of anemia, abnormal glucose tolerance test, reduced albumin and total protein levels, and amino acids quite diminished.
S151
CR PR SD PD PKW
Patients Hb (g/dl) (N)
Erythrocytes Leukocytes Lymphocytes Neutrophils Platelets (%) (103 cells/ml) (106 cells/ml) (103 cells/ml) (%)
9 10 18 19
4.64±0.54 4.35±0.49 4.38±0.55 4.19±0.65 <0.001
8.03±1.08 8.02±0.89 7.85±0.84 7.04±0.77 0.007
6.46±1.87 6.92±2.36 7.08±2.11 8.48±3.61 0.286
33.8±7.4 27.7±10.1 26.6±10.5 14.8±9.4 <0.001
53.8±10.1 61.3±10.7 60.6±12.3 73.1±13.4 0.006
299±98 228±61 252±72 337±170 0.093
Results: Hematology parameters are presented as mean ± standard deviation. The non-parametric Kruskal–Wallis test was used to detect significant differences. Post-hoc analysis with the least significant method was used to evaluate differences between groups. For all parameters with PKW < 0.01, the PD group was significantly different from all other groups. Conclusions: The significant positive correlations between PRRT outcome and baseline hemoglobin content, baseline erythrocyte cell count and baseline lymphocyte cell count are compatible with a cascade of free radical damage followed by immune activation. As the lymphocyte and neutrophil cell counts result from a differential white blood cell count, it is not surprising that we find an inverse correlation between PRRT outcome and neutrophil cell count. No correlation between PRRT outcome and leukocytes or platelets was found. Our results suggest that optimization of hemoglobin content prior to PRRT may be beneficial for therapy efficacy. No conflict of interest.